Inferential Optimization for Simultaneous Fitting of Multiple Components into a CryoEM Map of Their Assembly
Inferential Optimization for Simultaneous Fitting of Multiple Components into a CryoEM Map of Their Assembly
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DOI：
10.1016/j.jmb.2009.02.031
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发表时间：
2009-04-24
影响因子：
5.6
通讯作者：
Wolfson, Haim J.
中科院分区：
文献类型：
--
作者：
Lasker, Keren;Topf, Maya;Wolfson, Haim J.
大分子组装模型对于细胞过程的机械描述是必不可少的。这种模型越来越多地通过将组件的原子分辨率结构拟合到整个组件的密度图中来获得。然而，目前的密度拟合技术往往不足以明确确定所有组件的位置和方向。在这里，我们描述了MultiFit，一种用于同时将组件的原子结构以低至25埃的分辨率拟合到其组装密度图中的方法。根据评分函数对组件位置和方向进行优化，该评分函数包括地图中组件的拟合质量、组件从地图包络线的突出以及组件对之间的形状互补性。评分函数由我们的精确推理优化器DOMINO（多交互对象的离散优化）进行优化，该优化器有效地在离散采样空间中找到全局最小值。MultiFit以七个已知结构的组件为基准，每个组件由多达七个蛋白质组成。输入组分的原子结构从蛋白质数据库中获得，并基于16-99%的序列与模板结构的一致性进行比较建模。接近本机的配置通常是得分最高的模型。因此，MultiFit可以为电子显微镜描述的许多多组件组装结构的进一步细化提供初始配置。2009爱思唯尔有限公司版权所有。
Models of macromolecular assemblies are essential for a mechanistic description of cellular processes. Such models are increasingly obtained by fitting atomic-resolution structures of components into a density map of the whole assembly. Yet, current density-fitting techniques are frequently insufficient for an unambiguous determination of the positions and orientations of all components. Here, we describe MultiFit, a method used for simultaneously fitting atomic structures of components into their assembly density map at resolutions as low as 25 angstrom. The component positions and orientations are optimized with respect to a scoring function that includes the quality-of-fit of components in the map, the protrusion of components from the map envelope, and the shape complementarity between pairs of components. The scoring function is optimized by our exact inference optimizer DOMINO (Discrete Optimization of Multiple INteracting Objects) that efficiently finds the global minimum in a discrete sampling space. MultiFit was benchmarked on seven assemblies of known structure, consisting of up to seven proteins each. The input atomic structures of the components were obtained from the Protein Data Bank, as well as by comparative modeling based on a 16-99% sequence identity to a template structure. A near-native configuration was usually found as the top-scoring model. Therefore, MultiFit can provide initial configurations for further refinement of many multicomponent assembly structures described by electron microscopy. (C) 2009 Elsevier Ltd. All rights reserved.